rs3176767

chr19-10339075-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002162.5(ICAM3):c.77-127A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 998,410 control chromosomes in the GnomAD database, including 22,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3229 hom., cov: 32)
  • Exomes 𝑓: 0.21 (19411 hom.)
• Consequence: ICAM3 NM_002162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

Genes affected

ICAM3 (HGNC:5346): (intercellular adhesion molecule 3) The protein encoded by this gene is a member of the intercellular adhesion molecule (ICAM) family. All ICAM proteins are type I transmembrane glycoproteins, contain 2-9 immunoglobulin-like C2-type domains, and bind to the leukocyte adhesion LFA-1 protein. This protein is constitutively and abundantly expressed by all leucocytes and may be the most important ligand for LFA-1 in the initiation of the immune response. It functions not only as an adhesion molecule, but also as a potent signalling molecule. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047955513).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ICAM3	NM_002162.5	c.77-127A>C		intron_variant		ENST00000160262.10
ICAM3	NM_001320606.2	c.-282A>C		5_prime_UTR_variant	2/7
ICAM3	NM_001320605.2	c.77-127A>C		intron_variant
ICAM3	NM_001320608.2	c.-1024-127A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ICAM3	ENST00000160262.10	c.77-127A>C		intron_variant		1	NM_002162.5	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30752 AN: 151734 Hom.: 3231 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.192 AC: 19986 AN: 104130 Hom.: 1929 AF XY: 0.194 AC XY: 10722 AN XY: 55134

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.243

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.258

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.209 AC: 177266 AN: 846558 Hom.: 19411 Cov.: 11 AF XY: 0.212 AC XY: 91468 AN XY: 430894

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.202 AC: 30746 AN: 151852 Hom.: 3229 Cov.: 32 AF XY: 0.201 AC XY: 14949 AN XY: 74212

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.222

Alfa AF: 0.226 Hom.: 6930

Bravo AF: 0.198

TwinsUK AF: 0.217 AC: 805

ALSPAC AF: 0.236 AC: 908

ExAC AF: 0.144 AC: 16334

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.073
Dann	Benign	0.27
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0048	T
MutationTaster	Benign	1.0	P;P
GERP RS		-6.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3176767; hg19: chr19-10449751;